Hey ya'll. I am just about finished with a one month course of 40mg daily. A few days ago I started noticing that my nice thick hair was shedding at a much faster rate. Hairs falling out on my desk, computer, in the bathroom, etc.

I wasn't even aware that alopecia was a side effect of isotretinoin. No information in the medication insert, no info from my doctor, not even on the FDA website.

I came here, and have read through many of these posts on this thread and so my scholarly curiosity was aroused.

I did some research through my University's medical search tools and found some very interesting peer-reviewed journal studies that ya'll may be interested in... I haven't looked at the bulk of this thread so maybe ya'll are already aware of this but:

Below I have copy and pasted a study done by a team of Greek and Swiss researchers. Their goal was to measure the effects of isotretinoin on biotinidase levels. Biotinidase is the enzyme your liver produces to help break down biotin, which many of you have discovered may be related to the problem.

Some interesting notes, of 50 of the participants, 42 experienced hair loss. This is a staggering majority given that little information is out there about the side effect. Likewise, biotinidase levels were greatly curtailed, by as much as half, after only 30 days of isotretinoin treatment.

Background: Among the reaction and effectsof isotretinoin, mucocutaneous reactions, xerosisand erythema of the skin as well as elevationof liver enzymes and lipids excepthigh density lipoprotein have been reported.Objective: Since biotinidase is mainly producedin the liver and partial biotinidase deficiencycauses dermatological manifestations,seborrheic dermatitis, alopecia etc.,isotretinoin side effects in relation to biotinidaseactivity were studied. Methods: Fortytwo(n = 42) patients with severe cystic acnehad liver function tests, lipid estimations, serumbiotin as well as biotinidase activity evaluationsbefore (value 1) and on the 30thday (value 2) of treatment with isotretinoinmonotherapy (Roaccutane 0.5 mg/kg/24 h).The same laboratory tests were evaluated in50 controls only once. Moreover, the effect ofisotretinoin on a known plasma biotinidaseactivity was evaluated after incubation in vitrowith various concentrations of the drug.Results: A statistically significant elevation ofliver enzymes and lipids, except high densitylipoprotein, was observed at the end of thisstudy. On the contrary, biotinidase activitywas found to be significantly decreasedas compared to the initial values (value 1 =4.70 B 0.89 nmol/min/l, value 2 = 2.50 B0.8 nmol/min/l, p ! 0.001) and to controls(5.2 B 0.9 nmol/min/l vs. value 2 = 2.50 B 0.8nmol/min/l, p ! 0.001). Additionally, biotinlevels showed no significant alterations andthe in vitro incubation of the enzyme withvarious concentrations of the drug exhibitedno effect on its activity. Conclusion: It is suggestedthat isotretinoin isomers-metabolitesact in the liver, resulting in low biotinidaseactivity.

IntroductionThe use of orally administered isotretinoin(13-cis-retinoic acid) has transformed themanagement of patients with severe nodulocysticacne. Isotretinoin has marked effects onsebaceous glands and on sebum productionand composition [1, 2]. Of more significanceamong the reactions of the drug, mucocutaneousreactions, generalized itchiness and xerosis,increased skin fragility and exfoliationof palms and soles are encountered as adverseeffects of the drug [2]. Thinning of the hairtends to be more frequent in patients receivingisotretinoin whereas the usual ocular complicationsare mild and benign in nature [3â6]. Dyslipidemia, muscular and skeletal complications,minor transient abnormalities ofliver function have also been reported [7â9].Furthermore, biotinidase (EC 3.5.1.12)cleaves the biocytin moiety (lysyl biotin) andother small peptides present in biotin-dependentcarboxylases [10]. The enzyme permitsfree biotin to recycle and to be claimed fromdietary proteins. Biocytin, the lysine Ă-aminoamideof biotin, is thought to be the naturalsubstrate of biotinidase and probably arisesfrom the proteolysis of the biotin-dependentcarboxylases, in all of which biotin is bound tothe apocarboxylases via the Ă-amino group ofÂ·-lysine residue [11, 12]. Profound biotinidasedeficiency causes dermatological manifestationssimilar to biotin deficiency probably as aconsequence of impaired intestinal absorption,cellular salvage and renal reclamation of biotinas well as neurological manifestations includingseizures, hence little free biotin is metabolicallyavailable [12, 13]. Since inherited biotinidasedeficiency has been reported to induceskin lesions and conjunctivites, changes whichare also characteristic side effects of retinoids,it is speculated that these findings of acquiredbiotinidase deficiency of isotretinoin-treatedpatients should be investigated.Thus, the aim of this study was the evaluationof serum biotin levels as well as biotinidaseactivity in patients with cystic acne beforeand after 30 daysâ treatment with isotretinoin.Additionally, a preliminary in vitro experimentof isotretinoin effects on biotinidaseactivity was also carried out.Patients and MethodsPatientsForty-two patients with severe cystic acne (22 M,20 F), mean age 18.6 B 1.9 years, participated in thepresent study. Fifty medical students of comparableage and sex were the controls.

MethodsThe study was approved by the Greek EthicalCommittee. All patients and controls underwent laboratoryexaminations, complete blood counts, liverfunction tests, including SGOT, SGPT, alkaline phosphatase,ĂGt, total protein and lipids before (value 1)and after day 30 (value 2) of treatment with isotretinoinmonotherapy (Roaccutane Roche 0.5 mg/kg/24 hper os). Moreover blood (3.0 ml) was drawn for theestimation of biotin serum levels and biotinidase activityat the same intervals of this study (value 1 and value2). These laboratory tests were evaluated in controlsonly once. Biotinidase Assay. A fluorometric assay for thedetermination of biotinidase activity was carried out,according to Ebrahim and Dekisnamur [14]. Humanserum was dialyzed against 50 mM phosphate buffer,pH 7.0 and stored at â20Â° C prior to use. The reactionwas performed by adding dissolved serum sample to areaction mixture containing 0.1 M sodium acetatebuffer, pH 5.5, 5 mM EDTA, and 0.5 mM biocytin to afinal volume of 0.5 ml. After 1-hour incubation at37Â° C, 50 Ăl of perchloric acid 60% was added to stopthe reaction. The precipitated protein was removed bycentrifugation. To 0.45 ml of the supernatant, afteralkalination, 0.5 ml of fresh made buffer (containing0.5 M sodium carbonate, pH 9.5, 0.1% 1,2-diacetylbenzene and 3 mM 2-mercaptoethanol) was added.After 25 min at room temperature the samples wereread in a Perkin-Elmer LS3 fluorometer at 546 nm.Biotinidase activity was tested in triplicate under lightprotection when treated with isotretinoin (final concentration0.1â0.5 mM). The evaluation was carriedout after incubation at 37 Â° C and gentle shaking (drug,predissolved in ethanol absolute p.a.), against a blankidentical to control, a reference sample containing isotretinoinonly plus an ethanol reference blank (maximumisotretinoin absorbance at 354 nm). Pure isotretinoinwas purchased from Roche Hellas Ltd.Biotin Assay. An enzyme-linked method was usedto determine the biotin levels in serum, as previouslydescribed by Nyalala et al. [15].Statistical AnalysisStudentâs t test as well as Wilcoxon paired test wereutilized for the statistical analysis of the results.

ResultsObvious remission of their acne was observedin all (42/42), thinning as well as xerosisof the skin were found in 33/42 of ourpatients. Additional symptoms such as cheilitis(2/42), increased skin fragility and exfoliationparticularly of the palms (3/42) wereobserved, whereas 4 subjects (4/42) experiencedpatchy erythema of the forearms after30 days of treatment (table 1). As is shown in table 2, there was a statisticallysignificant elevation of liver enzymes(SGOT, SGPT, alkaline phosphatase, ĂGt)and lipids (cholesterol, triglycerides, LDL,VLDL); HDL was slightly reduced on the30th day on therapy. On the contrary, biotinidaseactivity (table 1) was greatly lowered butnot related to the observed skin lesions,whereas biotin serum levels showed no alterationat the same time (table 3). In addition,as presented in table 4, isotretinoin demonstratedno inhibitory effect on biotinidase activityeven when incubated with high concentrationsof the drug.

DiscussionIsotretinoin is associated with a high incidenceof a number of minor annoying sideeffects. The most common of these, occurringin most patients, is a characteristic cheilitis asfound in our patients; the lips become dry,scaly and cracked and may be the cause ofconsiderable discomfort. Other mucosal areasmay also become dry and uncomfortable.Slight soreness and peeling of the palms andsoles, also found in the patients, are seen butthese are not usually the cause of serious complaint.Of more significance, as far as thepatients are concerned, is the thinning of theirhair. This rarely results in a significant cosmeticdisability [1â4]. Apart from these rela-tively minor side effects isotretinoin is capableof causing serious toxic effects. Transientabnormalities of liver function have been reported.Increases of liver function tests aresaid to occur in patients on this drug [6â9].These findings were in agreement with thoseof our patients. Additionally up to 25% ofpatients on isotretinoin have been reported toexhibit an elevation of serum triglycerides,total cholesterol, LDL and decreased HDL [1,2, 8, 9]. These findings were also found in ourpatients. Furthermore, the decreased biotinidaseactivities (table 1, value 2), which werefound in our patients, were not related to theseverity of their presented skin side effects ofisotretinoin even though the number of patients who exhibited additional skin problemsother than thinning of hair and xerosis wassmall.According to the literature, neurologicaland ocular manifestations were mainly reportedin patients with profound (total) biotinidasedeficiency. The absence of suchsymptoms in our patients could be due totheir acquired âpartialâ biotinidase deficiencywhich was presented only with dermatologicalsymptoms [13]. Additionally, the highest specificactivity of biotinidase was found in liverand serum [10, 11], kidney and adrenalglands, but relatively low in the brain [15, 16].Pispa [17] noted a 50% decrease in the biotinidaseactivity in liver, and a 30% decrease inserum activity of partially hepatectomizedrats. It was concluded that the liver was thelikely source of serum biotinidase. Furthermore,the serum biotinidase activities in patientswith chronic hepatic diseases were detectedbelow the lower limit of activity foundin healthy adults [16â18]. Thus, it could besuggested that isotretinoin impairs the liverfunction [8], resulting in low biotinidase activityas it was previously reported [19]. Onthe other hand, the unaltered biotin serumlevels that were evaluated for the first timein patients with cystic acne before and after1-month treatment as well as the results of thein vitro experiments, which showed no directisotretinoin effect on biotinidase activity,could lead to the following preliminary suggestions.The absence of an in vitro effect ofthe drug on biotinidase could possibly be dueto physicochemical factors such as polaritysince isotretinoin was pretty insoluble in water.At this point it should be noted that therewas also no indication that any spectral isotretinoinproperties have interfered in the invitro assay. As regards the in vivo effect of isotretinointherapy, it seemed that isotretinoinisomers-metabolites, such as tretinoin, oxotretinoinor 4-oxo-isotretinoin, might play a pivotal role towards biotinidase activity [16].The latter hypothesis deserves to be investigatedthrough future experiments. However itcould be concluded that the dermatologicallesions (xerosis and thinning of the skin, cheilitis,erythema etc.), which were found in almostall the patients on treatment, could berelated to initial symptoms of their low biotinidaseactivities. These findings are clinicallyimportant since patients on isotretinoin treatmentmay develop symptoms similar to thoseobserved in patients with partial enzyme deficiency.Biotinidase deficiency is a potentiallytreatable disorder, and empirical evidencesuggests that a supplement of biotin (10 mg/day) in patients prevents its clinical manifestations[10]. Therefore, adequate biotinshould be prescribed as a supplement duringisotretinoin treatment in order to restore biotinidasefunction and offer more free metabolicallyavailable biotin.

To follow up, I further researched a claim in this article that referenced a 1985 study on the genetic form of biotinidase deficiency.

An infant began experiencing rabid symptoms from his biotinidase deficiency and the physician in this case prescribed daily megadoses of Biotin-Lysine (10 mg). Supposedly all symptoms were relieved from this.

Other posters have commented on taking a Biotin supplement. Any suggestions on your experience?

All I can say is that I hope I caught this side effect while it is still mild and hopefully it will end before it gets noticeably bad. (knocks on wood). The accutane was really doing great things for my acne too, even in such a short amount of time.

I am going to see my dermatologist on Monday and see what he thinks about all of this.